1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and have their apical surface in contact with tubular fluid and their basilar region in contact with the glomerulus. These cells sense changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubuloglomerular feedback) and renin release. 2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progress in this area has benefited from the use of the isolated perfused TAL-glomerular preparation, which permits direct access to MD cells. 3. Using microelectrodes to measure basolateral membrane potential (VBL) of MD cells, it was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150 mmol/L, VBL was found to depolarize by over 30 mV. 4. Basolateral membrane potential measurements were also used to identify an apical Na+:2Cl-:K+ cotransport pathway in MD cells that is the major pathway for NaCl entry into these cells. 5. Other work identified a basolateral chloride channel that is presumed to be responsible for changes in VBL during alterations in luminal [NaCl]. This channel, which is the predominant conductance across the basolateral membrane, may be regulated by intracellular Ca2+ and cAMP. 6. An apical Na+:H+ exchanger in MD cells was detected by measuring changes in intracellular pH using the fluorescent probe 2',7'-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein. 7. Using patch-clamp techniques, a high density of pH- and Ca(2+)-sensitive K+ channels was observed at the apical membrane of MD cells. 8. Other studies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20-60 mmol/L), reabsorption mediated by MD cells is very sensitive to changes in luminal [NaCl].

Although it is recognized that vasodilator-induced increases in renal plasma flow are not associated with increases in glomerular filtration rate (GFR), the mechanism responsible for the failure of GFR to exhibit plasma flow dependency under these circumstances remains uncertain. To evaluate this problem further, the effects of intra-arterial infusion of two vasodilators, bradykinin (n = 7) and papaverine (n = 6), on renal hemodynamics and glomerular function of dogs were determined. Both agents increased renal blood flow; however, GFR and single nephron GFR (SNGFR) remained unchanged during bradykinin infusion and decreased significantly during papaverine infusion. Transglomerular hydrostatic pressure and mean effective filtration pressure were not altered during bradykinin infusion but were significantly reduced by papaverine. Neither agent altered the glomerular filtration coefficient. These observations indicate that, in the dog, the GFR responses during renal vasodilation are dependent primarily on the effective filtration pressure.

The intrarenal tubuloglomerular feedback mechanism operates at the site of contact between the thick ascending limb and glomerulus where specialized macula densa cells detect changes in tubular fluid composition and transmit information to the smooth muscle cells of the afferent arteriole. Increases in tubular fluid osmolality result in the transmission of vasoconstrictor signals and decreases in the rate of filtrate formation. Recent studies have identified two sites at which cytosolic calcium may play important roles. First, studies indicate that tubuloglomerular mediated vasoconstriction involves calcium mediated excitation contraction coupling of smooth muscle cells of the afferent arteriole. This calcium mediated event is sensitive to calcium channel blockade. Second, recent studies suggest that the macula densa cells may detect changes in tubular fluid osmolality through a cytosolic calcium system. The use of intracellular calcium antagonists further suggests that intracellular calcium mobilization is the primary mechanism responsible for increases in macula densa cytosolic calcium with increases in tubular fluid osmolality. Calmodulin and cyclic AMP may serve as modulators of this cytosolic calcium system. These studies suggest that calcium plays important roles in the regulation of renal hemodynamics.

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